While epinephrine is the least concentrated of the catecholamines in mammalian brain, our view has developed that it has a significant role in regulation of sensory activation. This is thought to be due to its formation in extragranular sites, both intra and extraneuroally due to the compartmentalization of PNMT (phenylethanolamine N-methyltransferase). This view has prompted the study of the sites and cell types in which epinephrine may by synthesized. We have observed synthetic capacity in intrinsic neurons of the hypothalamus, incapable of storage of epinephrine as well as in tanycytes, the ependymal lining of the third ventricle. We have demonstrated that PNMT activity in the medulla is modified by stress while hypothalamic PNMT is relatively unaffected. Further, PNMT activity does not appear to be tightly linked to epinephrine content, suggesting that PNMT-containing neurons in the medulla are a subset of noradrenergic neurons. Inhibition of PNMT leads to motor activation and sensitivity to auditory cues in young rats, supporting the hypothesis of an inhibitory role for epinephrine in regulation of sensory activation.